Use of biomarkers in epidemiology: quantitative aspects

Cancer initiators (mutagens) present, due to the absence of definable no effect threshold, a special problem in toxicology, requiring a high sensitivity of detection methods. Disease epidemiology aiming at identification of carcinogens and quantification of associated risks has a low resolving power, the detectable incidence or mortality increments being often orders of magnitude larger than those which are of public concern. Other drawbacks of disease epidemiology is the long latency times and the influence of confounders. The use of genetic endpoints as biomarkers suffers from low cause specificity, although this drawback seems to be overcome, partly at least, by emerging methods for determination of mutation spectra at the DNA level. Proximal cancer initiators/mutagens are electrophilic compounds or metabolites that can react with nucleophilic atoms in nucleic acids and proteins. These reactions lead to 'adducts' that can be identified and quantified, e.g. in lymphocytes and erythrocytes in blood samples. The shift from biological observations to chemical analysis permits sufficient sensitivity, and measurement can be done shortly after onset of exposure. The well-defined life span of the adducts to hemoglobin (Hb) offer possibilities of dose calculation and risk estimation. For these reasons the measurement of adducts to Hb and DNA constitutes a powerful epidemiological tool, applications of which has been initiated in work environments and the general environment and also in the search for a priori unknown carcinogens.